Transfer RNA (tRNA) synthetase enzymes are of interest as potential targets for antibacterial agents. Mupirocin, a selective inhibitor of bacterial isoleucyl tRNA synthetase, is marketed for the treatment of skin infections and the eradication of nasal carriage of MRSA (methicillin-resistant Staphylococcus aureus) in hospital staff and patients.
Glycyl tRNA synthetase, a class I enzyme, is unusual in that its oligomeric structure varies depending on the organism from which it was isolated. Nucleic acid and amino acid sequences for glycyl tRNA synthetases are publicly available, including those of Thermus thermophilus, Mycoplasma genitalium, Homo sapiens, yeast, Bombyx mori and Caenorhabditis elegans, which are all characterized by a2 dimers, and Coxiella burnetti, Escherichia coli, Chlamydia trachomatous, Neisseria gonorrheae, Synechocystis sp., and Haemophilus influenzae, which are all characterized by being a2b2 tetramers.
There is a need in the art for novel tRNA synthetase enzyme active sites and catalytic sequences to enable identification and structure-based design of synthetase inhibitors, which are useful in the treatment or prophylaxis of diseases, particularly bacterial diseases caused by bacteria of the genus Staphylococcus, as well as other bacteria which may share catalytic domains with those of the genus Staphylococcus.